Chemical compounds that occur in nature have been an enormously valuable source of potential therapeutic agents for the treatment of many diseases. Following isolation from their source and purification, naturally occurring compounds may be used as active ingredients in pharmaceutical compositions. However, more commonly, derivatives or structural analogues of naturally occurring compounds become the active ingredients of pharmaceutical compositions. Although there are many instances of successful therapeutic treatments based on naturally occurring compounds, there remains a constant ongoing need for new and improved medicines. The search for natural products that may assist therefore continues.
Following the discovery of a class of compounds in which at least some members have potentially useful biological activity, there is usually a strong interest in the production of selected compounds from the class, initially for further development and ultimately for production on a large scale for marketing and sales. Production may be possible by simple isolation from a natural source, but typically this is not possible and synthetic or semi-synthetic processes are required to make sufficient quantities of the useful compounds.
One class of chemical compounds that has proven to be a rich source of compounds having biological activity is the furo[3,4-b]pyrans. Bioactive natural products incorporating the furo[3,4-b]pyran-5-one bicyclic system have been isolated from a variety of fungal sources. Fusidilactones A, B, D and E,1,2 massarilactones B and D,3-5 TAN-2483A and TAN-2483B,6 and waol A7-11 all contain this ring system. These fungal secondary metabolites display a variety of bioactivities, ranging from antibacterial to anti-tumour properties.
Syntheses of some members of the furo[3,4-b]pyran family of natural products, namely (−)-TAN-2483A, massarilactone B and waol A, are known.9-11 These natural products either incorporate a degree of unsaturation across the fused 4a-7a bond (e.g. massarilactone B and fusidilactone A) or possess a cis-relationship between H-2 and H-7a (e.g. (−)-TAN-2483A and waol A). In contrast to the other members of this family, (−)-TAN-2483B, isolated from a Japanese filamentous fungus,6 has a trans-relationship between H-2 and H-7a, and therefore presents different synthetic challenges.

(−)-TAN-2483A and (−)-TAN-2483B, isolated from fermentation of the filamentous fungus NR2329 (FERM BP-5905) in a culture medium, exhibit inhibition of c-Src (sarcoma) kinase and PTH-induced bone resorption. Therefore they have potential relevance to human pharmaceutics, including in cancer therapy and osteoporosis prevention or treatment. The synthesis of the furo[3,4-b]pyran core of (−)-TAN-2483B has been reported.12 The synthetic route is via a D-mannose-derived cyclopropane key intermediate. Employing this general synthetic methodology, the inventors have investigated the synthesis of analogues of (−)-TAN-2483B with the objective of then determining their biological activities in a range of assays and assessing their potential as pharmaceutical agents for treating certain diseases. The inventors have now found that analogues of (−)-TAN-2483B show inhibitory activity against a range of kinase enzymes and also inhibit the growth of certain cancer cell lines.
It is therefore an object of the invention to provide novel compounds and their use for treating diseases, or to at least provide a useful alternative to existing pharmaceutical treatments.